System for variably configurable, adaptable electrode arrays and effectuating software

ABSTRACT

Electrical non-invasive brain stimulation (NIBS) delivers weak electrical currents to the brain via electrodes that are affixed to the scalp. NIBS can excite or inhibit the brain in areas that are impacted by that electrical current during and for a short time following stimulation. Electrical NIBS can be used to change brain structure in terms of increasing white matter integrity as measured by diffusion tensor imaging. Together the electrical NIBS can induce changes in brain structure and function. The present methods and devices are adaptable to and configurable for facilitating the enhancement of brain performance, and the treatment of neurological diseases and tissues. The present methods and devices are advantageously designed to utilize modern electrodes deployed with, inter alia, various spatial arrangements, polarities, and current strengths to target brain areas or networks to thereby enhance performance or deliver therapeutic interventions.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 14/083,379 filed Nov. 18, 2013 which claims the benefit ofpriority to U.S. Prov. Pat. Apps. 61/796,634 filed Nov. 16, 2012 and61/962,698 filed Nov. 14, 2013, each of which is incorporated herein byreference in its entirety.

FIELD OF THE INVENTION

The present technology relates to the use of various electricalstimulation, variably configurable and adaptable electrodes andelectrode arrays, methods and software for affecting electricalcommunication systems that naturally occur in the brain, and foreffecting various kinds of advantageous neurological intervention, suchas redirecting learning processes. The various types and intensities ofelectrical stimulation may be adapted and arranged to amplify, or tocancel, targeted portions and functions of the brain. The technology hasnumerous uses, applications and embodiments.

BACKGROUND OF THE INVENTION

The application of electric fields or stimuli to the brain has beendemonstrated for a variety of neurological conditions, including thetreatment of psychological disorders. Attempts have been made to utilizesuch electrical stimuli to aid in the learning and teaching processes.However, many of the known methods involve invasive surgical proceduresthat carry considerable risk. While some non-invasive methodologies havebegun to show promise, novel devices, systems, networks and methods areneeded to address a variety of conditions and circumstances for whichelectrotherapies can be helpful. This is especially true in the teachingand scholarly fields, particularly as applied to personnel in thetherapeutic, intelligence and military education fields.

One method for applying electrical stimulation to regions of the brainto facilitate learning processes is Conventional Transcranial DirectCurrent Stimulation (c-TDCS). During a c-TDCS treatment, electrodes arepositioned on the head based on general knowledge about cognitiveprocesses and the location of the relevant brain structures that areinvolved. For example, working memory is the cognitive process thatallows us to hold information in memory for short periods of time. Theworking memory of a subject is one of the primary neurologicalrequirements when looking up, e.g., a phone number and remembering thatnumber until it is dialed. After the number is dialed, the workingmemory is typically cleared and the number is no longer remembered bythe person. A portion of the brain in the left, frontal region, i.e.,dorsal lateral prefrontal cortex (DLPFC) is reliably activated duringworking memory tasks as indicated by neuroimaging with, e.g., functionalmagnetic resonance imaging (fMRI), electroencephalography (EEG),magnetoencephalography (MEG), positron emission tomography (PET), singlephoton emission computed tomography (SPECT), and functional nearinfrared spectroscopy (fNIRS).

Thus, in a c-TDCS effort to facilitate working memory, one of theelectrodes (anode or cathode) is placed over the left frontal region ofthe subject's brain, and typically the other will be placed on the rightforehead. The c-TDCS approach generally results in 10%-20% gains in thelength of retention or the number of items that can be remembered.However, the c-TDCS approach and technology is limited and inapplicableto many circumstances for several reasons, including the ones iteratedbelow.

First, c-TDCS is an suboptimal approach to the problem of facilitatingcognition as c-TDCS uses general knowledge about the brain, the brain'scognitive functions, and the task at hand to target brain stimulation.Thus, methods and systems based upon c-TDCS are optimal, only when thetask at hand activates the same brain areas and utilizes the same brainfunctions as did many previous tasks. Hence, c-TDCS is limited orinapplicable when the details of brain function, in terms of variationbetween individuals and within individuals over time are considered.

Second, given that scientific endeavors try to push the frontiers ofknowledge, identical tasks are rarely repeated. Thus, c-TDCS does notaddress the circumstances when the problem to be addressed is new.Similar disadvantages pertain when a task is more complicated thanremembering a series of numbers. Decisions regarding the placement ofelectrodes to influence specific, task-related brain regions are alwaysnecessary in brain stimulation research and related methods to enhancehuman cognitive performance. With c-TDCS methods, the placement ofelectrodes is largely speculative.

Third, both the anode and the cathode have effects on brain activity.Placing for the anode and cathode on the head results in enhanced brainactivation in regions near the anode and suppressed brain activity inregions near the cathode. The combined enhancement in some brain regionsand suppression in others may have unintended consequences in terms offacilitating cognition and significantly complicates the interpretationof the extant data set. These disadvantages mean that c-TDCS is bothinaccurate and inapplicable in many circumstances.

Hence, methods for locating the particular regions of the brain to betreated and devices and methods for treating these locations aredesirable for the enhancement of human cognitive performance andtreatment of brain disease with non-invasive brain stimulation (NIBS).

SUMMARY OF THE INVENTION

The present technology includes several methods and devices wherebyneurological interventions are effected essentially by electricalNIBS-based procedures accomplished by the devices and methods describedherein. These methods and devices are provided to be directed towardspecific tasks, diseases, disorders and treatments. In one aspect, thesedevices and methods are adapted and arranged to be used on one or aplurality of subject brains for various purposes, affects and results.For instance, the devices and methods described herein provide methodsfor obtaining more accurate and dependable information that can begathered from the brains of subjects and for directing electrical NIBSto enhance cognitive performance, i.e. learning processes and functionsin the brain, and treating the symptoms and root causes of patients withbrain disease.

Furthermore, the NIBS methods described herein are guided by advancedneuroimaging methods that quantify the differences between healthybrains and patient populations or difference across time withinpopulations of individuals. The described method identifies patterns ofbrain activity or anatomy that underlie different brain states, modelsthe patterns of energy distribution in the brain from NIBS devices, andthen applies the NIBS device to alter behavior.

For instance, electrical NIBS is the first embodiment ofneuroimaging-guided non-invasive brain stimulation (ng-NIBS). However,the principles of ng-NIBS are readily expanded to include, e.g.,transcranial magnetic stimulation (TMS), repetitive TMS (rTMS), pulsedelectromagnetic fields (PEMF), transcranial alternating currentstimulation (TACS), transcranial random noise stimulation (TRNS), timevarying electrical stimulation (TVES), ultrasound brain stimulation(UBS), etc.

One method for applying NIBS is by utilizing Transcranial Direct CurrentStimulation (TDCS) which generally delivers a weak current to the brainvia electrodes that are affixed to the scalp of a subject. TDCS maytemporarily alter brain function for a short period of time whereperiods of brain function alteration may typically range anywhere from,e.g., 10 to 60 minutes, where the one or more areas of the brain thatare affected by TDCS are primarily dependent on the location of theelectrodes placed upon the patient's scalp.

One variation of the electrode housing assembly may have one or moreindividual electrodes arranged in various configurations within thehousing body for stimulating the underlying brain region through thepatient's scalp. To facilitate the electrical communication from theelectrodes to the brain, the electrodes may be housed within orsurrounded by an individual cavity or channel designed to hold a mediumsuch as electrically conductive gel (e.g., a pH buffered electrode gel)for facilitating the electrical transmission.

The electrodes are configured in circular shapes (e.g., toroid-shaped)arranged in a planar manner over the electrode housing; however, theelectrodes may be formed into other shapes. The electrode housing may befabricated from a variety of non-porous and non-electrically conductivematerials such as polymers or plastics. The toroid-shaped electrodeshave shown stability over the treatment time period and they do not leakerrant currents on the areas surrounding the skin-electrode interface.These electrodes also maximize the edge length to thereby reduceTDCS-elicited sensations at the skin-electrode interface. Each of theelectrodes may have a non-conductive material which is optionallypliable (e.g., rubber, silicone, etc.) surrounding each of therespective electrodes.

In use, the electrode housing may be positioned anywhere upon thepatient's scalp in proximity to the desired region for treatment, e.g.,along the side of the patient's head over the frontal, parietal,temporal, etc. region so long as the electrical stimulation from theelectrodes is transmitted through the scalp and into the targetedunderlying region of the brain. The region of the brain for treatmentmay be located using the targeting methods as described in furtherdetail herein. Additionally, the anodes and cathodes within theelectrode housing can be optionally varied or interchanged on the scalpto deliver varied combinations of anodal and cathodal current to theunderlying brain depending on the electrode arrangement or pattern toenhance the ability of the treatment procedure to precisely targetspecific structures within the brain.

Once the targeted region of the brain has been located, the electrodehousing may be positioned against the patient's head, e.g., over thefrontal or parietal region, and each of the electrodes may be filledwith the conductive gel (e.g., a pH buffered electrode gel) or medium tofacilitate electrical transmission. The electrode housing may be securedin place against the patient's head through various mechanisms.

In addition to the electrode assembly secured to the patient's scalp, anadditional electrode may be secured to a portion of the arm of thesubject, e.g., along the upper arm, back, shoulder, neck, or chest. Theelectrode secured to the non-scalp location may also be in communicationwith the controller as well.

The electrode-to-head connection impedance may vary from, e.g., 400 to40,000 ohms, and once applied this impedance may likely change over timeand across subjects within the 400 to 40,000 ohm range. When a constantcurrent stimulation is desirable and the electrodes have been desirablypositioned upon the patient's head, the electrical stimulation may beapplied in a ramped manner so that the current is not applied instantlybut is applied at an increasing level over a specified period of time.In the event that the impedance is detected to exceed 40,000 ohm, thecontroller may be programmed to automatically ramp down the stimulationover a specified period of time, e.g., 10 secs. An alert or alarm may beactivated and the device may be placed into a pause mode. Once treatmenthas been completed, the current may also be reduced at a decreasinglevel over a specified period of time. Ramping up and ramping down thecurrent may help to avoid any side effects affecting the user's skinand/or brain.

The electrode housing may optionally incorporate one or more sensorsand/or the controller may be programmed to monitor the impedance afterthe electrode housing has been applied to the patient's scalp. Before,during, and/or after treatment, the impedance may be monitored to detectfor changes in the impedance value. For instance, if a high impedance isdetected, the controller may be programmed to provide an alert or alarmto the user or practitioner and the device may automatically terminatethe electrical NIBS and/or related functions.

The electrical stimulation may be applied to the user where the initialcurrent, e.g., 0 mA, may be increased over a ramp up period until thetreatment level has been reached. The applied electrical stimulation maybe applied so that the treatment level is reached over a predeterminedperiod of time during the ramp up period so as to avoid any potentialinjury to the patient's tissue. For instance, the applied current may beincreased over a period of, e.g., 10 secs to 15 mins, during the ramp upperiod where the current may be increased at intervals of, e.g., 1 sec.

The electrical stimulation parameters may be changed or adjusted by thecontroller and the stimulation may be applied in a number of differentmodalities. For instance, the applied stimulation may be time varying inthe form of sinusoidal waves having a frequency of, e.g., 0 to 10,000Hz. Additionally, the stimulation may be adapted and arranged to allowfor the combination of sinusoidal waves to produce complex, time-varyingwaveforms that may mimic the activity and variability of a workingbrain.

The electrical stimulation may be applied at the treatment level for aspecified period of time over the treatment period which may rangeanywhere from, e.g., 0.1 mins to 60 mins, in 0.1 min increments. Thetreatment level may also range anywhere from, e.g., 0.1 mA to 4 mA,where the treatment level may be varied in, e.g., 0.1 mA increments. Thelength and intensity of the treatment may be controlled through thecontroller.

The practitioner may program the controller with the various treatmentparameters or they may be pre-set or controllable in real time via aremotely located controller. In the event that the controller iscontrolled remotely, communication to the controller may be maintainedthrough various wireless or wired modalities.

The controller may optionally include a user interface which allows forthe practitioner and/or patient to interface with the controller toenable the entry and/or display of various treatment parameters or theinterface may simply comprise simplified external controls, e.g.,controls which turn the treatment device on/off or pauses the treatment.

In the event the treatment system incorporates a pause mode to allow thepractitioner or user to temporarily pause a treatment session,stimulation may be resumed after the pause. The controller may beprogrammed to time out further treatment after a specified period oftime to prevent usage of the device beyond limits of frequency,amplitude, latency, or locations that are considered safe or effective.

After the treatment period, the stimulation may be reduced over a rampdown period until the initial current level has been reached or untilthe system has shut off. Like the ramp up period, the stimulation may bereduced over the ramp down period which may range anywhere from, e.g.,10 secs to 15 mins, during which the current may be decreased atintervals of, e.g., 1 sec. The controller may be optionally programmedto prevent the sudden starting or stopping of a treatment as a safetymeasure and to also ensure that the ramp up period and ramp down periodare sufficiently timed and stepped in intensity.

The controller may be optionally further programmed to lock-out anyfurther treatment once a treatment session has been completed for aspecified period of time, e.g., 2 hrs to 36 hrs or more. This featurecan be adapted and arranged in a number of different ways to limit useof the device to safe and effective treatment intervals.

Additionally and/or optionally, the controller may be further programmedto reverse the polarity of the electrodes along the electrode housingfollowing a treatment session to prevent corrosion of the connections ofthe individual electrodes.

In determining the location for placing the electrode array upon thepatient's head, c-TDCS generally involves utilizing only a generalknowledge about the brain, the brain's cognitive functions, and the taskat hand to target brain stimulation and is thus sub-optimal in locatingand treating specific regions of the brain.

All challenges associated with c-TDCS may be overcome by utilizingneuroimaging-guided TDCS (ng-TDCS) which assumes no prior knowledge ofthe different brain areas, cognitive processes and the task at hand.Generally, application of the ng-TDCS for treatment of the subject mayinvolve the steps of (1) recording the subject's brain activity atdifferent states, (2) evaluating the differences between the differentrecorded states, (3) virtualizing the difference image between therecorded states and modeling the placement of electrodes for NIBS tovisualize the currents for the purpose of optimally influencing theactivity of the brain regions that are differentially activated indistinct brain states, and then (4) stimulating the subject's brainaccording to the modeled image.

The recording phase of ng-TDCS empirically determines the task-relatedbrain regions or networks that should be targeted with ng-TDCS. Therecording of task related brain activity can be supported with one ormore neuroimaging modalities, e.g., magnetoencephalography (MEG),electroencephalography (EEG), functional magnetic resonance imaging(MRI), positron emission tomography (PET), single photon emissioncomputed tomography (SPECT), electrocorticography (ECOG), structuralmagnetic resonance imaging (sMRI), diffusion tensor imaging (DTI),magnetic resonance spectroscopy (MRS), functional near infraredspectroscopy (fNIRS), etc.

One embodiment could facilitate the transition from novice to expert.The brain activity is localized to the particular brain structure(s)that are activated in low performance states (e.g., novices) and highperformance states (e.g. experts). The images of the brain activitybetween the low performance states and high performance states are thensubtracted to produce a difference image that contains only the areas ofbrain activity that change between low performance and high performancestates.

The ng-TDCS technique takes advantage of the fact that there aredesirable brain states that lead to behaviors that are well suited tothe tasks and undesirable brain states that lead to poor performance onthe same tasks. Desired brain states that aide performance could beattentive, happy, expert, quick, or well rested, while comparableundesirable brain states might be inattentive, sad, untrained, slow,injured, or sleep deprived. The ng-TDCS technique uses data from, e.g.,MEG, EEG, fMRI, PET, SPECT, ECOG, fNIRS, sMRI, DTI, MRS, and othertechnologies to record data in the desirable and undesirable brainstates, and in one embodiment, maps the recorded brain activity to thestructures of origin using commonly available algorithms.

The localization of brain structures is done twice, once for desirableand again for undesirable brain states. This provides the basis forcomparing and contrasting the structural and functional brain statesthat contribute to the difference between performance with desirable andundesirable outcomes. Thereby, determining the target brain region(s)where the influence of electrical ng-NIBS could move the user from anundesired to a desired brain state. The ng-NIBS approach differs fromthe standard practice of electrical NIBS where neuroimaging is rarelyused determine target brain structures. When no neuroimaging isperformed the user must rely on often poorly founded assumptions aboutthe electrical NIBS and the brain.

For evaluating the differences between brain states, the ng-NIBStechnique calculates the target for electrical NIBS by comparing andcontrasting MEG, EEG. fMRI, PET, SPECT, ECOG, fNIRS, sMRI, DT1, MRS, andother techniques from two different brain states. In one embodiment, thecalculation could be made across individuals where a group ofindividuals with a desired brain state is compared to a group ofindividuals with an undesirable brain state; inattentive individualscould be compared to those who are attentive, expert individuals couldbe compared to novices, depressed individuals could be compared tohealthy subjects, brain injured individuals could be compared to healthyindividuals, individuals that perform a cognitive operation quicklycould be compared to those who work more slowly. This is a “one sizefits most” approach to the problem of optimizing NG-NIBS.

In yet another aspect, the present technology can employ various kindsof comparisons of various kinds of brain activities within the brain ofeach individual in order to determine the most advantageous locations orconformations of electrodes on the scalp. Multiple measures of brainactivity in desirable and undesirable brain states are recorded in eachindividual, the sources are localized with standard algorithms, and theimages of brain activity are subtracted to find the differences in brainactivity within an individual, not a group as described above, that canbe used to tailor an arrangement of scalp electrodes for optimaleffectiveness in each individual. For example, no two strokes are alike,no two traumatic brain injuries are alike, and no two cases of epilepsyare alike. Thus, customized arrangements of electrodes are necessary foreach individual. Further, there are individual differences in theorganization of healthy brains. Thus, the application of ng-NIBS can befurther optimized for cognitive enhancement, sleep aide, pain relief,and other brain functions by customized application for each individual.

Additional information derived from recorded brain activity along one ormore dimensions can be used to determine optimal ng-NIBS parameters forcognitive enhancement or treatment of disease and disorder. Theparameters that can be used to determine ng-NIBS type include, but arenot limited to, the location, amplitude, timing, phase, frequency, andduration of one or more activations in one or more brain areas.

The recorded brain activity is used not only to understand thecharacteristics of brain activity at specific brain regions but also togive information about the consistency or causation of amplituderelationships, time relationships, phase relationships, frequencyrelationships, and the duration relationships among and across multiplebrain regions in response to events in the environment that areprocessed by the brain.

However, the application of the ng-NIBS method to determine the optimalbrain targets for electrical NIBS is both innovative and extremelyuseful. The ng-NIBS approach allows both functional (e.g., MEG, EEG,fMRI, tNIRS, PET, SPECT, ECOG, and MRS) and structural (e.g., sMRI, DTI)comparisons between and within subjects. Previous studies have shownthat one type of electrical ng-NIBS alters both structural (DTI) byreducing radial diffusivity in white matter tracts on the stimulatedside of the brain and functional activity in terms of neurotransmitterturnover (MRS) as well as local and network level brain activity (MEG,EEG).

The difference image that will identify targets for stimulation withinthe brain can be derived by first determining the location of electricalactivity (MEG, EEG, fMRI, tNIRS, SPECT, PET, ECOG), chemicalconcentrations (MRS), and structures (sMRI, DTI) in the brain duringdesirable and undesirable brain states. Second, the brain scans fordesirable and undesirable brain states are coregistered for comparingsimilar spatial locations in the brain. Finally, the coregistered imagesof brain activity, chemistry, and/or structure, in desirable andundesirable brain states are subtracted. The difference image revealsthe locations of brain activity that differ functionally, chemically, orstructurally between desirable and undesirable brain states.

The difference image identifies regions of the brain that differ betweendesirable and undesirable brain states that may become targets forstimulation with electrical NIBS. Finite element modeling of a generichead or the head of an individual subject may be used to placeelectrical NIBS electrodes onto the head virtually using finite elementmodeling (FEM). The electrodes described herein can be placed on thevirtual head using FEM and can be moved to see locations in the brainthat are likely to be in the current path for electrical NIBS. Theposition of the electrodes described herein may be placed at locationson the scalp surface as to produce maximal current density in brainregions as indicated by FEM and identified as the target for stimulationby the difference image(s) in order to specifically task- or brain staterelated brain activity.

In some implementations a single electrode polarity may be placed on thescalp at difference image suggested scalp location(s), e.g., eitheranode to enhance brain activity or cathode to suppress brain activity.The other electrode may be placed on another portion of the subject'sbody, e.g., the upper arm, to eliminate problems caused by the placementof both anode and cathode on the scalp. This single scalp electrodeapproach straightforwardly enhances or suppresses brain activity withoutthe complicating effects of simultaneous excitation and inhibition ondifferent areas of brain. This ng-TDCS treatment can increase learningperformance by 100% rather than the 10%-20% commonly observed in c-TDCSexperiments.

In another embodiment, neuroimaging methods compare brain states withinindividuals across time, i.e. the brain states associated with correctresponses could be compared to those recorded during incorrectresponses, attentive could be compared to inattentive, novice could becompared to expert, tired could be compared to wide awake. Thecomparison of desirable and undesirable brain state within an individualcould be used to develop customized electrode arrangements forelectrical NIBS in each individual.

Electrical NIBS changes not only the activity of the brain but alsobrain anatomy. A 2011 report (van der Merwe et al., 2011) showed thatfractional anisotropy is increased primarily because of a decrease inthe radial diffusivity of water in the white matter tracts of the brain.This is typically interpreted as increased myelination and/or healthierwhite matter. This raises many possibilities for the uses of electricalNIBS in rehabilitation and white matter diseases of the brain that occurwith aging, Virchow-Robin Perivascular Spaces, deep white matterischemia, multiple sclerosis, progressive multifocalleukoencephalopathy, post-infections encephalitis, HIV relatedencephalitis, radiation injury, chemotherapy neurotoxicity (chemobrain),posterior reversible encephalopathy syndrome, central pontinemyelinolysis, the leukodystrophies and the adreno leukodystrophies, aswell as peripheral and central nervous system damage from traumaticbrain injury, concussion, chronic traumatic encephalopathy, spinal cordinjury, and stroke. All of these diseases could be treated with theembodiments that do comparisons across or within individuals to identifytargets for electrical NIBS in the CNS.

The idea of comparing and contrasting brain activity in two conditionsor across two populations is not novel. However, the use of advancedneuroimaging techniques to quantify difference between groups of people,including diseased and healthy populations, or within individuals acrosstime in combination with finite element modeling (FEM) and individuallyconfigurable electrode arrays to empirically guide electrical NIBSinterventions is quite novel. This electrical NIBS that evaluates thedifferences between desired and undesired brain states has been usedsuccessfully to double the rate of learning in multiple laboratories andon multiple tasks.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B show perspective and end views of one variation ofheadgear for supporting a magnetic stimulation delivery system upon apatient's head for applying non-invasive brain stimulation (NIBS).

FIGS. 2A and 2B show perspective views of one variation of a portablecompartment for storing various components, e.g., headgear, electricalstimulation delivery system, electronics, battery, etc. of the headgearof FIGS. 1A and 1B.

FIGS. 3A and 3B show perspective and end views of another variation ofheadgear configured to support a magnetic stimulation delivery systemrelative to the patient's head.

FIG. 3C shows a perspective view of another variation of a portablecompartment for storing the headgear of FIGS. 3A and 3B.

FIG. 4A shows a perspective assembly view of various components of theelectrical stimulation delivery system.

FIG. 4B shows a perspective view of a controller to which the electrodeassembly may be connected.

FIGS. 5A and 5B show top and side views of one variation of theelectrical stimulation delivery electrode housing.

FIG. 6A shows a bottom view of one variation of the electrode housingillustrating the electrode configuration.

FIGS. 6B and 6C show top and bottom views of the electrode housing withthe wire assembly.

FIGS. 7A to 7C show top, perspective, and side views of anothervariation of the electrode housing where the assembly may be comprisedof electrode components which are reconfigurable relative to oneanother.

FIGS. 7D to 7F show top views of various configurations in which theindividual electrode components may be reconfigured into alternativepatterns.

FIG. 7G shows a bottom view of the reconfigurable electrode housingillustrating the electrode configuration.

FIGS. 8A and 8B show variations for positioning the electrode housingupon the head of a patient utilizing headgear.

FIG. 9A shows another view of the electrode housing positioned upon thepatient's head for targeting predetermined regions of the brain.

FIG. 9B shows another variation of the electrode housing for positioningrelative to the patient's head.

FIG. 10 shows a schematic illustration of a system block diagram for a1-channel variation in which each channel provides an independentcurrent source across two electrodes.

FIG. 11 shows a graph illustrating one example for applying thestimulation to the patient.

FIG. 12A shows a graph illustrating the differences in target detectionand identification between treatment sessions when applying activeelectrical stimulation and sham stimulation.

FIG. 12B shows a graph illustrating the difference between activeelectrical stimulation and sham stimulation over time.

FIG. 13A shows a flow chart of one method for utilizingneuroimaging-guided non-invasive brain stimulation.

FIG. 13B shows a flow chart illustrating specific examples for utilizingneuroimaging-guided non-invasive brain stimulation.

DETAILED DESCRIPTION OF THE INVENTION

According to the many and various embodiments of the present technology,the present disclosure provides, inter alia, various devices, methods,networks and systems for providing therapeutic and/or beneficial cranialelectro-stimulation. Accordingly, the present disclosure providesmethods, systems, software and apparatus that utilize a combination ofreal time brain functional monitoring and non-invasive electrical and/ormagnetic trans-cranial brain stimulation to modify the brain function asexhibited in individual and group activities.

The present technology includes several methods and devices wherebyneurological interventions are effected essentially by electricalNIBS-based procedures accomplished by the devices and methods describedherein. These methods and devices are provided to be directed towardspecific tasks, diseases, disorders and treatments. In one aspect, thesedevices and methods are adapted and arranged to be used on one or aplurality of subject brains for various purposes, affects and results.For instance, the devices and methods described herein provide methodsfor obtaining more accurate and dependable interventions based oninformation that can be gathered from the brains of subjects and fordirecting learning processes and functions in the brain and treating thepatients accordingly.

One method for applying electrical NIBS is by utilizing TranscranialDirect Current Stimulation (TDCS) which generally delivers a weakconstant current to the brain via electrodes that are affixed to thescalp of a subject. Electrical NIBS can also take the form ofalternating current, randomly varying currents, temporally patternedcurrents, or combinations of the aforementioned. Electrical NIBS may beapplied for various lengths of time (typically 10-60 minutes) totemporarily alter brain function. Electrical NIBS can alter thefunctions of one or more areas of the brain that are primarily dependenton the location of the electrodes placed upon the subject or patient'sscalp.

Electrodes

Conventional TDCS (c-TDCS) units are large, boxy, table-top deviceswhich are provided with multiple external controls and are suitable forlaboratory use but problematic for the dissemination and use of thetechnology to greater numbers of people. In one aspect, the TDCS systemsdescribed herein may comprise a small, portable, programmable TDCS unitthat may be adapted and arranged to provide one or more programmablefunctions. Various aspects of the systems are designed to enhance thesafety and usability of the product by many people.

The application of TDCS may be used to change (e.g., for a short periodof time) the way the brain of a subject works. TDCS applied to the headof a subject accomplishes this by delivering a very weak electricalcurrent through the scalp and into the brain. One method for applyingthe TDCS may include securing one or more electrodes to the scalp by anumber of different modalities. For instance, FIGS. 1A and 1B showperspective and end views of one variation of headgear 101 which can beused to facilitate placement of the one or more electrodes relative tothe patient's head. The headgear 101 shown may be configured to be wornupon the patient's head like a pair of glasses where the headgear 101may have a frame supported by two stabilizing ear loops 102 and a nosebridge 103. Once folded, the headgear 101 may be configured for compactstorage, as shown in FIG. 1B, where the ear loops 102 may be foldedrelative to the nose bridge 103.

FIG. 2A illustrates a perspective view of an optional storage housinghaving a top lid 201 and bottom lid 202 with features or projections 203which define a receiving channel or region for holding variouscomponents of the TDCS system, e.g., headgear, electrode assembly,electronics, power supply, etc. FIG. 2B illustrates a perspective viewof various components of the TDCS system positioned within the storagehousing. For instance, the headgear 101 may be folded and secured via astrap 204 upon the top lid 201 while an electrode assembly 205 havinginterface plugs 206 may be stored within the feature 203.

FIGS. 3A and 3B show perspective and end views of another variation ofheadgear which is configured to facilitate the positioning of the one ormore electrodes relative to the patient's head. This variation mayinclude headgear 101 frame supported by two stabilizing ear loops 102and a nose bridge 103, as previously described. Additionally, thisvariation may further incorporate one or more hinged joints 300, 301which connect to corresponding stanchions 303, 304 which may extend fromthe joints and away from the frame such that the stanchions 303, 304 aresuitably positioned relative to the patient's head for holding electrodeor electrode array against selected regions of the scalp. Each of thestanchions 303, 304 may be configured to be uniform in length or theymay be varied depending on the region of the scalp where the electrodeis to be positioned. Moreover, one or more of the stanchions 303, 304may be adjustable in length to allow for variability of electrodepositioning. Furthermore, one or more of the stanchions 303, 304 may becurved or angled to allow for additional variability in electrodepositioning.

When the stanchions 303, 304 are not in use such as when the headgear isstored, the stanchions 303, 304 may be folded via the hinged joints 300,301 to allow for the stanchions 303, 304 to be folded for storage. FIG.3C shows a perspective view of another variation of the storage housinghaving a top lid 305 and bottom lid 306 with features or projections 307which define a receiving channel or region for holding variouscomponents of the TDCS system, as similarly described above. Thisvariation illustrates an example of the headgear of FIG. 3B secured tothe top lid 305 via a strap 308 and the electrode assembly 309 withinterface plugs 310 stored within the receiving channel or region of thebottom lid 306.

FIG. 4A shows a perspective assembly view of some of the variouscomponents of the magnetic stimulation delivery system which may beincorporated into the TDCS system. A controller 401 may have a userinterface for setting various delivery stimulation parameters, poweractuator, one or more various indicators or alarms for alerting theuser, etc. One or more wires or cables 403 may connect the controller401 to the electrode housing 402 which may be secured to the patient'shead.

The controller 401 may be powered by an external power supply or it mayoptionally incorporate an internal battery either within the controller401 or separately attached. The controller 401 may thus be programmed tomonitor the battery charge level to ensure that the device is capable ofcompleting the treatment stimulation at the same charge level. One ormore alerts or alarms may be included in the controller 401 to providean indication of charge level or the information may be provided on auser interface.

Another variation of the controller 404 is illustrated in theperspective view of FIG. 4B. The housing of the controller 404 maycontain the electronics and processor as well as power supply. Theelectrode assembly may be coupled to the controller 404 via a connector405 and one or more control inputs 406 may also be incorporated into thecontroller 404.

One variation of the electrode housing assembly 501 may be seen in thetop and side views shown respectively in FIGS. 5A and 5B. In thisvariation, the electrode housing 501 may have one or more individualelectrodes 503 arranged in various configurations within the housingbody 502 for stimulating the underlying brain region through thepatient's scalp. To facilitate the electrical communication from theelectrodes to the brain, the electrodes may be housed within orsurrounded by an individual cavity or channel designed to hold a mediumsuch as electrically conductive gel (e.g., a pH buffered electrode gel)for facilitating the electrical transmission.

For instance, FIG. 6A shows a bottom view of the electrode housing 601having a bottom surface over which the individual electrodes 603 may bearranged. The electrodes shown are configured in circular shapes (e.g.,toroid-shaped) arranged in a planar manner over the electrode housing601; however, the electrodes 603 may be formed into other shapes. Theelectrode housing 601 may be fabricated from a variety of non-porousmaterials such as polymers or plastics. The toroid-shaped electrodeshave shown stability over the treatment time period and they do not leakerrant currents on the areas surrounding the skin-electrode interface.These electrodes also maximize the edge length to thereby reduceelectrical NIBS-elicited sensations at the skin-electrode interface.Each of the electrodes 603 may have a non-conductive material 602 whichis optionally pliable (e.g., rubber, silicone, etc.) surrounding each ofthe respective electrodes 603. As further illustrated in the respectivetop and bottom views of FIGS. 6B and 6C, each electrode 603 may beconfigured in a circular shape which defines an opening 604 through andwhich is electrically coupled to a respective wire 606.

With the electrodes positioned along the bottom surface, thenon-conductive material 602 may surround the electrode 603 and extendfrom the bottom surface to form a cavity or channel 605 having a depthof about, e.g., 4 mm, which may be optionally filled with a sufficientvolume of a conductive gel (e.g., a pH buffered electrode gel) or mediumto facilitate transmission of the electrical stimulation into theunderlying scalp. The opening 604 in the center of the electrode 603 andthe air spaces around the electrodes 603 are desirable for access to theskin surface to ensure a low impedance interface between skin andelectrode.

The variation shown in FIGS. 6B and 6C illustrate five electrodes 603which are arranged in a uniform circular pattern over the electrodehousing 601. However, other variations may have the electrodes 603arranged in other patterns as needed. Moreover, the electrode housing601 may be designed to be portable so that the housing has a dimensionof, e.g., 1 cm×1 cm up to 4 cm×4 cm or greater, and a height of, e.g.,up to 4 cm.

In use, the electrode housing 601 may be positioned anywhere upon thepatient's scalp in proximity to the desired region for treatment, e.g.,along the side of the patient's head over the frontal, parietal,temporal, etc. region so long as the electrical stimulation from theelectrodes is transmitted through the scalp and into the targetedunderlying region of the brain. The region of the brain for treatmentmay be located using the targeting methods as described in furtherdetail herein. Additionally, the anodes and cathodes within theelectrode housing 601 can be optionally varied or interchanged on thescalp to deliver varied combinations of anodal and cathodal current tothe underlying brain depending on the electrode arrangement or patternto enhance the ability of the treatment procedure to precisely targetspecific structures within the brain.

Another variation of the electrode housing is shown in the top,perspective, and side views of FIGS. 7A to 7C which illustrate anelectrode housing 701 which is formed by several individual electrodecomponents 701A to 701E which are attachable to one another in variousconfigurations. In the variation shown, each of the electrode components701A to 701E may have a corresponding electrode 702 and the electrodecomponent may be formed to have uniform circular sector shape whichcollectively together form a circular electrode housing 701. Theelectrode components may be attachable to an adjacent electrodecomponent along a component interface 703 via any number of securementmechanisms. Accordingly, the electrode housing 701 with each of theelectrode components 701A to 701E may be used as an electrode assemblywhen positioned in proximity to the scalp.

Alternatively, one or more portions of the electrode components 701A to701E may be separated and rearranged relative to one another to formdifferent configurations for positioning in proximity to the scalp fortreatment. FIG. 7D shows a top view of one alternative arrangement 701′in which components 701C, 701D, 701E may be attached to component 701Bin a reversed configuration. FIG. 7E shows another variation 701″ whereeach of the electrode components may be attached to an adjacentcomponent in an alternating pattern and FIG. 7F shows yet anothervariation 701′″ where individual components may be separated and usedindividually. These variations are intended to be illustrative ofpotential arrangements and other variations are intended to be includedwithin the scope of this description.

FIG. 7G shows a bottom view of the electrode housing 701 when formed ina circular configuration and having a bottom interface surface 704 overwhich the individual electrodes 706 may be arranged. The electrodes 706shown are configured in circular shapes (e.g., toroid-shaped) arrangedin a planar manner with a non-conductive material 705 surrounding theelectrode 706 and extending from the bottom surface to form a cavity orchannel 707.

The designing and configuring of the individual electrodes and arrays ofelectrodes can be accomplished by applying finite element modeling (FEM)to data gathered regarding the brain, scalp, skull and associatedtissues. In this aspect, the finite element model can be adapted andarranged to function as a guide with respect to the influence of theelectrical NIBS on one or more portions, regions or areas of one or moretarget brain regions. With the gathered data, and with the assistance offinite element analysis, the relative configuration(s) and design(s) ofthe electrodes and electrode arrays can be effected with respect tovarious brain tissues in terms of, for example, the spatialdistribution, polarity, and intensity of the excitation or inhibitiondelivered via NIBS. The combination of these systems, methods, devices,components and elements of the present technology are directed toward anefficient and effective step or activity of stimulating one or moretarget brains with electrical NIBS. As another advantage, one or more ofthe polarity, intensity, and spatial distribution of stimulation can beprogrammed into the devices and arrays described herein to producemaximal influence (excitation or inhibition) at the target sites.

Once the targeted region of the brain has been located, the electrodehousing 801 may be positioned against the patient's head PT, e.g., overthe frontal or parietal region as shown in the side view of FIG. 8A, andeach of the electrodes may be filled with the conductive gel (e.g., a pHbuffered electrode gel) or medium to facilitate electrical transmission.The electrode housing 801 may be secured in place against the patient'shead through various mechanisms, e.g., the headgear 802 shown secured tothe patient's head via the loops 803 and optional band 805. Theelectrode housing 801 may be seen with the electrical wires or cables804 coupled to the housing 801 and to a controller.

Optionally, the electrode housing 801 may incorporate a pressureactivated switch which requires the user or practitioner toaffirmatively press the electrode housing 801 against the patient'sscalp. Once the pressure switch is activated, the controller 501 may beprogrammed to automatically begin the intervention or treatmentstimulation.

FIG. 8B shows a perspective view of the patient PT with headgear 101with the one or more stanchions 304 extending from the frame. In thisexample, the electrode housings 701 in its circular configuration areattached to the end of stanchions 304 for positioning relative to thepatient's scalp. In other variations, the electrode housing 701 may berearranged and/or separated, as described above, and secured to one ormore stanchions 304 as desired for positioning over various regions ofthe scalp.

FIG. 9A shows another side view of another variation of the electrodehousing 701 positioned upon the patient's PT scalp at a treatmentlocation 901, e.g., over the frontal or parietal region (depending uponthe region of the brain to be stimulated). The electrodes 703 may beseen arranged upon the electrode housing 701 in a uniform circularpattern (e.g., five-electrode array) with each electrode 703 beingsurrounded by the corresponding non-conductive material 702. Such anarrangement may be suitable for delivering the stimulation to a focalarea of the brain. The cavity or channel 705 formed around eachelectrode 703 may be optionally filled with a conductive gel or medium,as described herein, to facilitate electrical contact with theunderlying scalp for transmission of the stimulation signals into thebrain regions below.

FIG. 9B shows another variation of an electrode assembly 902 which isformed into a cross or X-shaped pattern (e.g., five-electrode array).While the electrode pattern shown in FIG. 9A was arranged in a compactpattern where each electrode 703 was positioned adjacent to one anotherin a circular arrangement, the arm members 903 of the electrode assembly902 shown in FIG. 9B has its arm extending from a common intersection904 such that the intersection 904 is centered over the treatmentlocation 901 and the arm members 903, shown in this example as four armsextending perpendicularly relative to on another, extend over differentregions of the patient's head so as to position their respectiveelectrodes 703 at corresponding different regions of the brain. Anelectrode 703 may be positioned near or at the terminal end of each armmember 903 as well as near or at the intersection 904 and each of theelectrodes 703 may be configured to incorporate the non-conductivematerial 702 for forming the cavity or channel, as previously described.The electrode assembly 902 may be secured against the patient's scalpusing any of the methods described and while the arm members 903 areshown to have a uniform length, one or all of the arm members 903 may bevaried in length depending upon the region of the brain to bestimulated. Such an arrangement may be suitable when delivering thestimulation over a relatively wider area of the brain rather than afocal area.

In addition to the electrode assembly secured to the patient's scalp, anadditional electrode may be secured to a portion of the arm, chest,back, or neck of the subject, e.g., along the upper arm. The electrodesecured to the arm may also be in communication with the controller 501as well.

Controller

Generally, the controller may be used to drive, e.g., 24 independentchannels, where each channel provides an independent current sourceacross an electrode pair where the voltage level is controlled by anarbitrary waveform that is input into the controller, e.g., read fromflash memory or other storage. The stored treatment data may comprise atleast one arbitrary waveform that determines a number of differenttreatment parameters, e.g., frequency, amplitude, latency, location, andduration of the stimulation. The start of any operation of the systemmay be based on an external trigger event and the maximum voltage levelsas well as time duration for stimulation may be controlled prior thestart of any stimulation. That is, the maximum voltage for each channelmay be determined at the beginning of the stimulation based, at least inpart, on a measured impedance value in each channel so as to inhibit orprevent a relatively high current from being delivered to the subject.Hence, the current and voltage across each electrode may be monitoredindividually and each channel may drive an arbitrary waveformindependently of one another. Moreover, because the system allows forthe controller to select either bi-polar or single-ended outputs, theselection of a bi-polar output enables the use of a floating groundwhich allows for any arbitrary channel to be grounded and thus allowsfor the delivery of any desired input waveform.

Furthermore, with respect to the trigger event, the controller may beconfigured to receive multiple trigger inputs for responses toneuroimaging or behavioral data individually or in combination with orwithout Boolean logical responses to brain and behavioral state of thesubject. In particular, the multiple trigger inputs for responses may bewith respect to brain or behavioral state of a collocated or remotelylocated individual.

As the current is driven across the electrodes the current, voltage, andan open circuit detect circuit may monitor the stimulation. A schematicsystem block diagram 1000 is shown for a single channel for illustrativepurposes in FIG. 10. The controller may house the electronics for eachof the channels including the control processor 1002, which mayinterface with a host computer 1001 (or other device). New stimulationwaveforms, log files, system control and setup, etc. may be input orotherwise performed by the computer 1001 which interfaces with thecontrol processor 1002.

For each channel, the control processor 1002 may send the data to adigital-to-analog converter (DAC) 1003 to control the output from thevoltage source 1004 to the corresponding electrode pair 1005 whenpositioned into proximity with the target. A potentiometer or variableresistor 1006 may be electrically coupled with a voltage amplifier 1007which in turn is electrically coupled to the processor 1002 via ananalog-to-digital converter (ADC) 1008 to provide feedback to theprocessor 1002. An open circuit detection circuit may be incommunication with the processor 1002 from the electrode pair 1005 andvia a voltage amplifier 1009 and an analog-to-digital converter (ADC)1010, as shown, for determining whether an open circuit is present. Thecurrent read by the ADC across each electrode may be, e.g., 1 mA, whilethe voltage across each electrode may be, e.g., 10 V. The impedancevalue across each electrode may be calculated by the RMS of resistancesover a 1 second interval:

$\begin{matrix}{V_{rms} = \sqrt{\frac{\sum\limits_{n = 1}^{w}\left( V_{n} \right)^{2}}{w}}} & (1)\end{matrix}$

where w equals the 1 second window.

The controller may output a maximum of, e.g., 80V (+/−40V), which may beadjusted by the software to maintain a current over anelectrode-to-scalp connection impedance range from, e.g., 4 to 40,000Ohms. For this reason, a current source is desirable where a frequencyrange for DC may range up to 10 kHz. The impedance of the system may bemonitored and checked automatically by the controller, e.g., once perminute, and the mean impedance may be calculated across the entireelectrode array. Additionally, the impedance values may be monitored andmeasured for each channel independently of one another. Because of thepossible hardware and software combination, the current and voltagespecifications on individual channels do not need to sum to zero thusallowing current steering across a plurality of channels where the totalcurrent sums to zero.

With the electrodes desirably positioned upon the patient's head, theelectrical stimulation may be applied in a ramped manner so that thecurrent is not applied instantly but is applied at an increasing levelover a specified period of time. In the event that the impedance isdetected to exceed 40,000 Ohm, the controller 501 may be programmed toautomatically ramp down the stimulation over a specified period of time,e.g., 10 secs. An alert or alarm may be activated and the device may beplaced into a pause mode. Once treatment has been completed, the currentmay also be reduced at a decreasing level over a specified period oftime. Ramping up and ramping down the current may help to avoid anydamage to the patient's brain.

The electrode housing 701 may optionally incorporate one or more sensorsand/or the controller 501 may be programmed to monitor the impedanceafter the electrode housing 701 has been applied to the patient's scalp.Before, during, and/or after treatment, the impedance may be monitoredto detect for changes in the impedance value. For instance, if a highimpedance is detected, the controller 501 may be programmed to providean alert or alarm to the user or practitioner and the device may beautomatically terminated. Furthermore, the current output may bemaintained via a hardware control loop and also monitored via a softwarecontrol loop.

FIG. 11 shows a graph illustrating one example for applying theelectrical stimulation to the patient where the initial current 1101,e.g., 0 mA, may be increased over a ramp up period 1103 until thetreatment level 1102 (e.g., X mA) has been reached with an outputconstant current maximum of, e.g., 4 mA peak magnitude. The appliedelectrical stimulation may be applied so that the treatment level 1102is reached over a predetermined period of time during the ramp up period1103 so as to avoid any potential injury to the patient's tissue. Forinstance, the applied current may be increased over a period of, e.g.,10 secs to 15 mins, during the ramp up period 1103 where the current maybe increased at intervals of, e.g., 1 sec. An example may includeramping the current up and/or down each over a 15 sec period althoughthe ramp up and/or ramp down period may be adjustable.

The electrical stimulation parameters may be controlled by thecontroller 501 and the stimulation may be applied in a number ofdifferent modalities. For instance, the applied stimulation may be timevarying in the form of sinusoidal waves having a frequency of, e.g., 0to 10,000 Hz. Additionally, the stimulation may be adapted and arrangedto allow for the combination of sinusoidal waves to produce complex,time-varying waveforms that may mimic the activity and variability of aworking brain.

The electrical stimulation may be applied at the treatment level 1102for a specified period of time over the treatment period 1104 which mayrange anywhere from, e.g., 0.1 mins to 60 mins, in 0.1 min increments.The treatment level 1102 may also range anywhere from, e.g., 0.1 mA to 4mA, where the treatment level may be varied in, e.g., 0.1 mA increments.At the higher end of voltage, the current may be ramped downwards to,e.g., 2 mA. The length and intensity of the treatment may be controlledthrough the controller, e.g., controller 501. The practitioner mayprogram the controller with the various treatment parameters or they maybe pre-set or controllable in real time via a remotely locatedcontroller. In the event that the controller 501 is controlled remotely,communication to the controller 501 may be maintained through variouswireless or wired modalities. The controller 501 may optionally includea user interface which allows for the practitioner and/or patient tointerface with the controller 501 to enable the entry and/or display ofvarious treatment parameters or the interface may simply comprisesimplified external controls, e.g., controls which turn the treatmentdevice on/off or pauses the treatment.

The controller may also be configured to wirelessly transmit data toand/or receive data from a device which is located remotely from thecontroller. Hence, the controller may transmit data sensed from theelectrodes as well as receive data from the remote device, e.g.,computer, laptop, tablet, smartphone, etc., such as treatmentparameters, power levels, stimulation waveforms, etc. Moreover, thiscommunication may occur through various wireless protocols, e.g.,internet, cellular, RF, etc. As the controller may be configured with anetwork interface, this interface may be configured to remotely receiveservicing or activation signals in response to brain or behavior states.All wired inputs to the controller including the charger, trigger, andnetwork lines will be optically isolated to protect the person receivingthe stimulation from voltages transferred from the wall socket.

In the event the treatment system incorporates a pause mode to allow thepractitioner or user to temporarily pause a treatment session,stimulation may be resumed after the pause. The system may be configuredto wait for a predetermined period of time following the initiation ofthe pause mode after which treatment resumes automatically or thetreatment may be resumed after being affirmatively re-started by thepractitioner.

After the treatment period 1104, the stimulation may be reduced over aramp down period 1105 until the initial current level 1001 has beenreached or until the system has shut off. Like the ramp up period 1103,the stimulation may be reduced over the ramp down period 1105 which mayrange anywhere from, e.g., 10 secs to 15 mins, during which the currentmay be decreased at intervals of, e.g., 1 sec. The controller 501 may beoptionally programmed to prevent the sudden starting or stopping of atreatment as a safety measure and to also ensure that the ramp up period1103 and ramp down period 1105 are sufficiently timed and stepped inintensity.

The controller 501 may be optionally further programmed to time-out orlock-out any further treatment once a treatment session has beencompleted for a specified period of time, e.g., 2 hrs to 36 hrs or more.This feature can be adapted and arranged as a safety feature in a numberof different ways to limit use of the device to safe treatmentintervals.

Additionally and/or optionally, the controller 501 may be furtherprogrammed to reverse the polarity of the electrodes 703 when placed inthe electrode housing 701 following a treatment session as maintenanceto prevent corrosion of the connections of the individual electrodes andpreserve the useful life of the electrodes 703.

Treatment (Neuroimaging-Guided Noninvasive Brain Stimulation)

Generally, application of the electrical stimulation for treatment ofsubjects or patients may involve the steps of (1) recording thesubject's brain activity at different states, (2) evaluating thedifferences between the different recorded states, (3) finite elementmodeling of the current paths in the brain to target brain state uniqueactivations identified in the difference images from neuroimaging, andthen (4) stimulating the subject's brain according to the modeled image;otherwise known as a ng-NIBS technique.

In determining the location for placing the electrode array upon thepatient's head, c-TDCS generally involves utilizing only a generalknowledge about the brain, the brain's cognitive functions, and the taskat hand to target brain stimulation and is thus sub-optimal in locatingand treating specific regions of the brain. Hence, all the challengesassociated with c-TDCS may be overcome by utilizing neuroimaging-guidedTDCS (ng-TDCS) which assumes no prior knowledge of the different brainareas, cognitive processes and the task at hand. Moreover, ng-TDCSempirically determines the brain areas that are involved in theperformance of the task by measuring task-related brain activity withone or more neuroimaging modalities, e.g., magnetoencephalography (MEG),electroencephalography (EEG), functional magnetic resonance imaging(fMRI), positron emission tomography (PET), single photon emissioncomputed tomography (SPECT), electrocorticography (ECOG), structuralmagnetic resonance imaging (sMRI), diffusion tensor imaging (OTT),magnetic resonance spectroscopy (MRS), functional near infraredspectroscopy (fNIRS), etc.

The brain activity is localized to the particular brain structure(s)that are activated in low performance states (e.g., novices) and highperformance states (e.g. experts). The images of the brain activity inthe low performance states and high performance states are thencoregistered and subtracted to produce a difference image that containsonly the areas of brain activity that change between low performance andhigh performance states.

The ng-TDCS (and related electrical, magnetic, optical, and ultrasonicNIBS methods) technique takes advantage of the fact that there aredesirable brain states that lead to behaviors that are well suited tothe tasks and undesirable brain states that lead to poor performance onthe same tasks. Desired brain states that aide performance could beattentive, happy, expert, quick while comparable undesirable brainstates might be inattentive, sad, untrained, or slow, injured. ng-TDCSuses data from, e.g., MEG, EEG, fMRI, PET, SPECT, ECOG, fNIRS, sMRI,DTI, MRS, and other technologies to record data in the desirable andundesirable brain states, and in one embodiment, maps the recorded brainactivity to the structures of origin in the brain using commonlyavailable algorithms.

The mapping to brain structures is done twice, once for desirable andagain for undesirable brain states. This provides the basis forcomparing and contrasting the structural and functional brain statesthat contribute to the difference between performance with desirable andundesirable outcomes. Thereby, determining the target brain region(s)where the influence of electrical NIBS could move the user from anundesired to a desired brain state. The ng-NIBS approach differs fromthe standard practice of electrical NIBS where neuroimaging is rarelyused determine target brain structures. When no neuroimaging isperformed the user must rely on often poorly founded assumptions aboutboth the current paths in electrical NIBS and task-related brainactivity.

This difference image is fed into a finite element model that can beused to accurately calculate the path of electrical currents through thehead as they pass between electrical NIBS electrodes where at least oneis placed on the scalp. The electrodes described herein may be placed atlocations on the scalp that pass maximal current density through targetbrain tissues that differentiate brain state and task related brainactivity. A single electrode polarity may be placed on the scalp at thislocation, e.g., either anode to enhance brain activity or cathode tosuppress brain activity. The other electrode may be placed on anotherportion of the subject's body, e.g., the upper arm, to eliminateproblems caused by the placement of both anode and cathode on the scalp.This aspect straightforwardly enhances or suppresses brain activitywithout any complicating effects of both electrodes on the scalp.Utilizing this ng-TDCS treatment can increase learning performance by100% rather than the 10%-20% commonly observed in c-TDCS experiments.

For evaluating the differences between brain states, the ng-NIBStechnique calculates the target for electrical NIBS by comparing andcontrasting MEG, EEG. fMRI, PET, SPECT, ECOG, fNRS, sMRI, DT1, MRS, andother techniques from two different brain states. In one embodiment, thecalculation could be made across individuals where a group ofindividuals with a desired brain state is compared to a group ofindividuals with an undesirable brain state; inattentive individualscould be compared to those who are attentive, expert individuals couldbe compared to novices, depressed individuals could be compared tohealthy subjects, brain injured individuals could be compared to healthyindividuals, individuals that perform a cognitive operation quicklycould be compared to those who work more slowly. This is a “one sizefits most” approach to the problem of optimizing ng-NIBS.

In another embodiment, neuroimaging methods compare brain states withinindividuals across time, i.e. the brain states associated with correctresponses could be compared to those recorded during incorrectresponses, attentive could be compared to inattentive, novice could becompared to expert, tired could be compared to wide awake. Thecomparison of desirable and undesirable brain state within an individualcould be used to develop customized electrode arrangements for ng-NIBSin each individual.

In yet another aspect, the present technology can employ various kindsof comparisons of various kinds of brain activities with respect to thesame brain in order to determine the most advantageous locations orconformations of electrodes. Thus, the analyses of one or more brainactivities that are used to determine the correctly positioned orconformed electrodes and arrays of electrodes for delivering electricalNIBS can include many different parameters. Such parameters include, butare not limited to, the location, amplitude, timing, phase, frequency,and duration of one or more activities in one or more brain areas. Therecorded brain activity thus obtained is especially useful when the datarecorded gives information about the consistency or causation ofamplitude relationships, time relationships, phase relationships,frequency relationships, and the duration relationships across multiplesimilar events processed by the brain, or across regions in the brain.However, the application of this method to determine the optimal braintargets for electrical NIBS is both innovative and extremely useful. Theng-NIBS approach allows both functional (e.g., MEG, EEG, fMRI, tNIRS,PET, SPECT, ECOG, and MRS) and structural (e.g., sMRI, DTI) comparisonsbetween and within subjects. Previous studies have shown that one typeof electrical NIBS, TDCS, can alter measures of DTI that indicate thewhite matter tracts in the brain have decreased radial diffusivity inthe hemisphere ipsilateral to stimulation.

This is typically interpreted as increased myelination and/or healthierwhite matter. This raises many possibilities for the uses of electricalNIBS in rehabilitation and white matter diseases of the brain that occurwith aging, Virchow-Robin Perivascular Spaces, deep white matterischemia, multiple sclerosis, progressive multifocalleukoencephalopathy, post-infections encephalitis, HIV relatedencephalitis, radiation injury, chemotherapy neurotoxicity (chemobrain),posterior reversible encephalopathy syndrome, central pontinemyelinolysis, the leukodystrophies and the adreno leukodystrophies, aswell as peripheral and central nervous system damage from traumaticbrain injury, concussion, chronic traumatic encephalopathy, spinal cordinjury, and stroke. All of these diseases could be treated with theembodiments that do comparisons across or within individuals to identifytargets for electrical NIBS in the CNS. The idea of comparing andcontrasting brain activity in two conditions or across two populationsis not novel. However, evaluating the differences in advancedneuroimaging techniques between populations in order to guide electricalNIBS is quite novel. This approach has been used successfully to doublethe rate of learning in multiple laboratories and on multiple tasks.This allows for evaluation of the differences between desired andundesired brain states.

Furthermore, the ng-TDCS is a method that could be expanded to includedifferent types of brain stimulation. For instance, ng-TDCS becomesneuroimaging-guided non-invasive brain stimulation (ng-NIBS) and theprinciples of ng-NIBS could be expanded to include, e.g., transcranialmagnetic stimulation (TMS), repetitive TMS (rTMS), pulsedelectromagnetic fields (PEMF), transcranial alternating currentstimulation (TACS), transcranial random noise stimulation (TRNS), timevarying electrical stimulation (TVES), ultrasound brain stimulation(UBS), etc. Moreover, the various hardware and software combinations mayallow for the channels to operate with independent or common referencesto create TDCS, TACS, TRNS, and TVES presentable in any combinationacross single or multiple channels.

In recording the brain activity of a subject's brain, the step or actionof (1) recording brain activity (data) may be accomplished by any one ormore imaging modalities, as described herein, during desirable andnon-desirable brain states. Examples of desirable brain states which areuseful for practicing the present methods include: attentive, expert,healthy, uninjured, cognitively fast, and cognitively flexible. Examplesof undesirable brain states include: inattentive, untrained, depressed,brain injured (such as TBI), cognitively slow, cognitively rigid.

In another aspect, one embodiment of a method of the invention includesthe step or action of (2) evaluating the differences in the subjectbrain or brains between desirable and non-desirable brain states. Thisdifference evaluation is performed with respect to the brain activitydata obtained by one or more of the initial steps or actions of thisembodiment of the method of the invention. The results of thisdifference evaluation between desirable and non-desirable brain statescan then be used to determine portions, regions or parts of the subjectbrain or brains which are suitable targets for electrical NIBS. Byeffecting NIBS of these target parts of the subject brain or brains,brain circuitry can influenced to transition from an undesirable to adesirable state. The advantages of this transition can be numerous.

In yet another aspect, the data obtained in the present method can beused to (3) virtualize the differences between the desirable andnon-desirable brain states to effect a determination of one or moreadvantageous electrode array designs and configurations which aresuitable for specific desired purposes, such as the teaching oflanguages, the enhancing of decision making, the increasing ofvigilance, the increasing of cognitive flexibility, the enhancing ofcreativity, the teaching of the correct accents for languages, theincreasing of attention, the enhancing of sleep. the reversing of braindamage (such as that associated with traumatic brain injury, stroke,concussion, hypoxia, and chemical or other injury), and the treating ofsymptoms of mental illness (i.e. reducing hallucinations, elevatingmood, alleviating flattened affect, reducing anxiety, reducing insomnia,reducing unwanted memory, enhancing social skills, reducing repetitivethoughts, reducing social phobias).

With the present technology, electrodes and electrode arrays can bedesigned and configurations of arrays as described herein, including howthe electrodes communicate with one another and with other components ofthe invention, can be effected to maximize the effectiveness ofNIBS-based neurological interventions. Such designs and configurationscan be effected with respect to, among other factors, spatial positionsof the electrodes in two or more dimensions, the respective polaritiesof the electrodes, the timing of activity on or between electrodes, thefrequency (typically in terms of Hz) delivered by one or moreelectrodes, the frequency of stimulation in terms of repetition of adetermined stimulation regimen, the latency of the stimulation, if any,on an electrode or electrodes with respect to environmental events, thecorrelation among stimulation parameters across electrodes, thecorrelation of stimulation with environmental events, the phaserelationships among stimulation parameters across electrodes, theduration of stimulation on an electrode or electrodes and therelationships of these durations across electrodes, causal inferencesfrom recordings of activity that are replayed to the brain via anelectrode or electrodes, and the intensity or intensities of theelectrical stimulation delivered by the respective electrodes, such thatthe NIBS stimulations can have the greatest desirable influence ontargeted brain areas.

With respect to the effects of the ng-TDCS stimulation treatment, FIG.12A illustrates graph 1201 which shows experimental sample results ofsubjects who have performed a target detection and identification taskbefore and during the application of electrical stimulation withng-TDCS. The task results from an un-stimulated control group 1202 isshown at a baseline, after a first test (Test 1), and after a secondtest (Test 2), where stimulation was not applied at all. A second groupwas tested at the baseline, after Test 1 where no stimulation wasapplied 1203 (i.e., sham), and after Test 2 where stimulation wasapplied 1204. The number of True Positives/False Positives increasedaccordingly from the no stimulation 1203 to when stimulation was applied1204. Likewise, a third group was tested at the baseline, after Test 1where stimulation was applied 1205, and after Test 2 where nostimulation was applied 1206. Accordingly, the number of TruePositives/False Positives decreased from when the stimulation wasapplied 1205 to when no stimulation was applied 1206.

Furthermore, additional experiments of subjects have shown that theeffect of ng-TDCS stimulation has lasting residual effects after thetreatment has ended. For instance, FIG. 12B shows a graph 1207 whichtracked the results of enhanced brain function between a first group ofsubjects 1208 during ng-TDCS stimulation, 10 min. post TDCS stimulation,40 min. post TDCS stimulation, and 50 min. post TDCS stimulation. Thisis compared to a second group of subjects 1209 which had a shamtreatment applied and who were tested over the same time periods.Accordingly, the first group 1208 showed a significant change inmagnitude over the second group 1209 who had a sham treatment appliedfor a period of time even after the stimulation has ended.

FIG. 13A illustrates a flow chart showing the various steps in furtherdetail for applying a ng-TDCS treatment. Initially, a target problem maybe chosen 1301 which may involve identifying a target problem fornoninvasive brain stimulation and then developing a training program ortherapeutic intervention for the identified target problem. The brainmay then be imaged at both the low performance level and the highperformance level 1302. This step may include recording the brainactivity at the beginning of the training or intervention using anynumber of various neuroimaging modalities. The training or interventionmay be continued to a desired end point and the brain activity may berecorded at the end of the training or intervention period again usingany number of various neuroimaging modalities.

Once the brain has been imaged, the differences in the brain activity atthe high and low performance levels 1303 may be examined. This includeslocalizing the brain regions that are activated at the beginning and endof the training or intervention and then calculating a difference imageby subtracting the brain activity at the beginning from the activity atthe end. The difference image may be entered into finite elementmodeling (FEM) software 1304 (e.g., SIMULIA, Dassault Systemes or othersimilar FEM software) which may be used to model the distribution ofcurrent from electrical NIBS in the brain of the subject. With the knowncurrent distribution, the electrodes may be positioned on the scalp atlocations that pass the maximum current through target structures 1305using electrical ng-NIBS during, e.g., a training program or therapeuticintervention.

According to some preferred specific embodiments of the presenttechnology, an EEG, fMRI or MEG device is used to measure the location,amplitude, and magnitude of time dependent electric and/or magneticfield oscillations that are recorded as one or more outputs or responsefrom the brain in various circumstances. These oscillations thatindicate neural activity can be related to normal functions such as thesleep cycle, pattern recognition, learning, teaching, various types ofcommunications and decision making. These signals can also be indicativeof abnormal functions caused by sleep deprivation, stress, epilepsy,autism, addiction, and stress disorders.

In another key aspect, users of the present methods, devices and arrayscan determine the influence of electrical NIBS to a brain or a group ofbrains. By way of example, after a target for electrical NIBS isdetermined in the Recording and Evaluation phases of ng-NIBS, theamplitude, polarity, and spatial location of the electrodes that havethe greatest influence on the brain structure(s). This is accomplishedwith finite element modeling. In one aspect, finite element modelingdivides the brain, scalp, skull, and surrounding tissues into differentlayers that can be used to make predictions about the path thatelectrical NIBS will take through the tissues that surround the brain toget to targeted brain structures. The finite element models aregenerated from high resolution sMR. The different gray levels in sMRIimages are due to different concentrations of water in the tissues. Thedifferent gray levels allow the tissues to be segmented into separatelayers and tissue compartments. The layers and tissue compartments arethen tessellated across the surface with triangular meshes.

The tessellated meshes can then be assigned a value for how wellelectricity is conducted through the volume of tissue. Collectively, thelayers and tissue volumes in the finite element model are called theforward model. In ng-NIBS the area(s) of the brain identified as targetsfor stimulation to enhance desirable brain states will be virtuallyactivated in the finite element model. The virtual activation of thebrain area will project electricity through the forward model and ontothe scalp surface. The identified areas of the cortical surface will bethe locations for the spatial position of the electrodes. The polarityof the currents that are shown on the scalp will determine the polarityof the currents that are delivered at each spatial position. Thestrength of the current that is projected onto the scalp surface willdetermine the proposition of the total current that is delivered at eachelectrode position.

While the finite element model is used to target the brain structures,it is not used to target the regions of maximum current on the scalp.Rather, the electrodes may be moved around the scalp until the currentpassing through the target brain structure is maximized. That is, FEM isused to determine where the underlying current is passing through thebrain structure and FEM helps to iterate which brain regions areaffected for targeting and determining the ultimate electrodepositioning relative to the scalp.

Another aspect is that the present methods can be used to target eithergray matter (the parts of the brain containing the parts of the neuronsthat perform the computations necessary for sensation, perception,cognition, emotion, movement, thought, and other behaviors) or the whitematter (the connecting tissue between specialized parts of the brainthat work together to produce sensation, perception, cognition, emotion,movement, thought, and other behaviors).

FIG. 13B illustrates a flow chart with examples of the various steps infurther detail for applying an ng-TDCS treatment. In choosing a targetproblem 1311, one example illustrates how enhancing a subject's responseto touch may be approached by, e.g., stimulating the subject's mediannerve in combination with ng-NIBS. The subject's brain may be imaged atboth the low performance level and the high performance level 1312 byfirst recording the subjects brain activity with any of the neuroimagingmodalities, then stimulating the median nerve with pulses at the wristthat are below threshold for producing sensation and then recording thesubject's brain activity again with stronger pulses that aresuprathreshold.

The differences in the subject's brain at both the sub- andsuprathreshold performance levels may then be examined 1313 where thedifference image may be calculated by subtracting the localized activebrain regions between the high and low sensation levels, as illustratedby the difference images at the respective median nerve stimulationlevels.

This resulting difference image may be entered into FEM software 1314which may then be used to model the distribution of current in thesubject's brain as a result of electrical NIBS, as illustrated. With theknown current distribution, the electrodes may be adjusted in positionrelative to the scalp 1315 until the current passing through thetargeted brain structure is maximized and the subject's brain may thenbe non-invasively stimulated in a targeted manner using any of themethods and devices described herein.

Stimulation of one or a plurality of brains with electrical NIBSprovides manifold advantages and uses. In yet an additional aspect ofthe present technology, the pattern(s) of stimulation that can bedesigned to stimulate brain regions that will increase the likelihood ofa desired brain state from the recording and localizing of brainactivity, creation of the difference image, and use of the finiteelement modeling (FEM) portions of ng-NIBS can be programmed into adevice of the invention as described herein. Such programming willtypically utilize 5 to 10 electrodes on the scalp surface and up to 5extracephalic electrodes, although any number of electrodes can beadapted to the present devices and methods. The lengths of the up to 10curved plastic arms that hold the electrodes will be tailored to theposition on the scalp that is necessary to target the ng-NIBS determinedbrain structure. The angle at which each aim need to leave the headframe will be set by a mechanism of grooves that locks the arms into theappropriate angle. The polarity and amplitude of electrical NIBS will beset to mimic the pattern observed in the finite element model.

The tailoring of the arm length and the setting of amplitudes andmagnitudes can be determined from data collected across individuals orwithin an individual and for targeting structure or functionaldifferences between desired and undesired brain states. The electricalNIBS device is now programmed to facilitate a one specific desirablebrain state or structure. The device would need to be reprogrammed andnewly tailored for producing a different desirable brain state. The listof desirable brain states is very large but several specific exampleswill be given below.

Another useful and innovative with respect to the present technologycomprises one or more methods for determining the appropriate target forelectrical NIBS in the brain. At present, conventional methods fordetermining the brain region(s) to be targeted with electrical NIBS arelargely based on textbook descriptions of cognitive functions and/orwork that details functions that are lost after strokes or brainlesions. Determining target brain tissues with this “lesions andliterature” methodology makes multiple fallacious assumptions. Theseinclude: 1) all brains are the same, 2) loss of function with lesionindicates the location of function, 3) the area of brain directlyunderneath the electrode is most effected by the electrical NIBS, and 4)laboratory tasks are good proxies for the activities of daily Life interms of brain activation and prediction of success. The methodsdisclosed herein in one or more embodiments can be individualized, andcustomized or matched to appropriate patterns of brain activity, anddeployed into daily life to enhance desirable behaviors and reduceundesirable behaviors by electrical NIBS that enhances or reducesactivity in appropriate brain regions.

In another embodiment it can be configured in a “one size fits most”configuration that is not designed to be individualized. In bothembodiments, the method requires recording brain activity duringdesirable and undesirable conditions or responses. The patterns of brainactivity or structure in the desirable and undesirable conditions arethen compared to glean the location and direction in which brainactivity or structure must be changed to move from an undesirable to adesirable state of performance. In one embodiment, the effects ofelectrical NIBS on the brain can then be determined with finite elementmodels that use electrodes in various spatial configurations, strengths,and polarities to determine the most favorable arrangement of aplurality of electrodes that will maximally effect the brain region(s)that is being targeted to alter behavior or deliver therapeuticintervention through excitation or inhibition or structural change.

The optimal spatial configuration, strength, and polarity can then beimplemented on the device described above to apply stimulation to thebrain to enhance performance or provide therapy through brainexcitation, inhibition or structural change. ng-NIBS is distinct fromthe lesions and literature approach in multiple ways. 1) There are no apriori assumptions made about the location(s), strength(s), or temporalcharacteristics of brain activity or structure. 2) ng-NIBS uses brainstates associated with different behavioral patterns in an individual orgroup of individuals to determine the appropriate brain areas fortargeted stimulation. 3) ng-NIBS makes no apriori assumptions about howthe effects of electrical NI BS are distributed in the brain; it modelsthem virtually. 4) ng-NIBS is readily amenable to individualization(ing-NIBS) to not only to specific persons but also to specific brainstates within a person as they vary across the day when the embodimentrecords activity and delivers stimulation as part of a single device.

In one aspect, the time dependent electric field oscillations providethe measurements to one or more devices or networks of the invention,which are able to interpret the measurements, identify signals that areindicative of an abnormal or undesirable function, and generate amodified signal that can be transmitted into the brain using atrans-cranial brain stimulator such as transcranial Direct CurrentStimulation (tDCS), transcranial alternating current stimulation (tACS)or Transcranial Magnetic Stimulation (TMS) in order to produce a desiredeffect. As one example of one specific embodiment of the numerousembodiments of the present invention, if the detected brain output isindicative of the onset of an undesirable brain process, such as theinitial stage of a seizure, then the signal generated by the device anddelivered to the brain would provide an in-phase, equal magnitude, butopposite sign in order to cancel that signal through destructiveinterference with the output signal. This superposition of an oppositesign (or cancelling) signal is similar in some aspects to known methodsof acoustic noise cancellation commonly used in active acoustic noisecancellation headphones and speakers. Accordingly, a unique feature ofthe inventions provided in this disclosure is the application of one ormore “cancellation signals” within the brain region generating theundesirable output signal.

The application of a pulsed, oscillating, or DC electric field to modifyneural activity is known in the art. These approaches typically apply astimulus in an on/off manner based on a prescribed dose/timerelationship. In stark contrast, according to various embodiments, thepresently described invention may utilize closed loop feedback in orderto provide active modification of a device-generated input signal inresponse to the brain's output signal.

According to another embodiment of the invention, a feedback device isconnected to electrodes that are place on the head in locations that areoptimized for activation or deactivation of signals of interest that areproduced by the brain. For instance, if the output is indicative of theearly stage of a seizure in a localized brain region, the electrodes arelocated to provide or direct a cancellation wave to the part of thebrain responsible for generating the early stage seizure related signalsin order to prevent the growth of wide spread coupled brainoscillations. According to various embodiment s, at least a portion ofthe feedback device could take the form of a headset, cap, hat, helmet,head draping, headband or pillow. For instance, the headgear 802 shownabove in FIG. 8 may incorporate such a feedback device.

According to yet another embodiment, the feedback device could be placedand optimized to encourage the brain to generate particular signals, orcycles of particular signals, that are adapted and arranged to fulfillone or more desired functions. For example, a suitable applicationenvisaged by the inventor is to treat sleep deprivation caused byundesirable rapid transition from non-REM sleep into REM sleep. In thisone of many embodiments, the purpose of the input field would be toentrain the signals produced by the brain that are associated withhealthy sleep cycles and reduce the frequency of maladaptive patterns ofsleep. In one alternative, the feedback device could be designed toencourage restorative slow wave sleep and prevent quick or prematuretransition into REM sleep. Control of sleep brain patterns, either bypreventing undesirable signals or by controlling the signal patternsover time could help reduce or prevent nightmares, and/or produce sleepthat is more restorative over shorter durations, essentially allowingfor an electrically stimulated powernap. Similar patterns could beprofoundly useful for treatment of disorders such as post-traumaticstress disorder (PTSD).

Alternatively stated, the feedback device could be designed such thatone or more electrodes are placed so as to direct the feedbackdevice-generated signal towards those regions of the brain (the targetregions. portions or structures) that are responsible for generating thesignal of interest. In some embodiments, arrays of electrodes may beutilized to localize or concentrate feedback device-generated signals toone or more specific regions (the target regions, portions orstructures) of the brain.

According to still another embodiment, the feedback device could beplaced and optimized not to cancel an undesirable signal, but rather toamplify a desirable, naturally occurring signal. In yet anotheralternative of some of the key present methods, the feedback devicecould cancel or suppress some signals of interest, while amplifyingothers. For example, in applications (methods) to enhance memory,learning, or pattern recognition, the detection of a desirable signalwould allow the feedback device to amplify that signal associated withstorage of the information of interest separately, or in concert, withsuppressing cognitive processes that compete for resources that could beused to encode memory.

For example, in one embodiment adapted for the purpose of teaching oneor more languages, the brain activity and structure of one or moresubject groups are recorded with one or more neuroimaging methods withrespect to both desirable and undesirable brain states defined as fluentand non-fluent, respectively, according to the present methods. Thedifferences between the desirable and undesirable states are thenevaluated in order to produce an electrode array that will facilitatelanguage learning in many individuals.

As an aspect of teaching languages, individual enhancement strategiescan be tailored, developed or customized to one or a group of people. Asan example of certain parameters of methods of the invention, the brainactivity and structure-of a single subject can be recorded in desirableand undesirable brain states. The data thereby obtained can be used, forexample, to determine and teach such nuances of language learning suchas inflection, accent and rhythm. The difference between such desirableand undesirable brain states can advantageously be evaluated to producean electrode array that is customized to enhance performance in aparticular individual and may or may not be applicable to otherindividuals.

Similar strategies can be applied to many different types of learningdynamics. Thus, general aspects of the present methods can be applied tothereby achieve numerous different learning scenarios. As additionalexamples, the present methods, techniques and procedures, with thebenefit of the present specification, can be directed toward thereduction of fatigue, of either an individual or a group.

According to yet another embodiment, two or more feedback device couldbe in electrical communication with one another. In such embodiments, afeedback device of a first individual could transmit information to thefeedback device of another individual or to the feedback devices of agroup of individuals in order to enhance team performance bymanipulating attention, engagement, and/or coordination of the group.

In one of many possible military applications involved in a small groupattempting to deal with ambiguous unstructured information, the couplingof multiple feedback devices would lead to enhanced detection ofrelevant information and coordination of the group. For example, if thefeedback device of one member of a group identified brain wavesassociated with increased alertness, for example in response to theindividual noticing “unusual or suspicious activity,” the feedbackdevices of the other members of the group could be programmed toincrease alertness for all members of the group within a predeterminedproximity, or those who are chosen to be in a particular communicationsnetwork.

According to another embodiment, the individual feedback device could becoupled to remotely located computers to provide additional real timeprocessing and memory for each of the feedback devices. These computerscould then be connected into a feedback and control system to provideoverall management and coordination of the ensemble. For example, thefeedback devices could be used to enhance the performance of a team ofcyber defenders who are dealing with rapidly changing ambiguousinformation. The ability to detect pre-conscious patterns is known inthe art, and the sharing of these preconscious detections would enhancethe speed and coordination of the group. The ability to amplify thisdetection capability of the individuals and the group would lead tosubstantial performance enhancements of both the individuals, and of thegroup as a whole. According to yet another embodiment, rather thangenerating a signal that is equal and opposite to the signal ofinterest, the feedback device could introduce white noise so as todisrupt the signal of interest.

In accordance with the several objects of the invention, a variablyconfigurable electrode array is provided, wherein the array comprises:at least two electrodes, wherein each of the electrodes is operationallyconnected to the other electrodes, or to at least one microprocessor; ahousing adapted and arranged for variably positioning the electrodeswith respect to one another, and for variably positioning each of theelectrodes respectively in operational proximity to one or more regions,areas or points of a scalp of a subject upon which the array is placed;at least one microprocessor located in operational proximity to thehousing, wherein the microprocessor is adapted and arranged to processdata collected by means of the electrodes; and at least one data storagemodule located in operational proximity to the array, wherein the moduleis adapted and arranged to be operationally connectable to one or moreof the at least two electrodes and the at least one microprocessor; andsoftware suitable for storing software, wherein the software is adaptedand arranged for one or more of operating one or more functions of thearray, storing data collected by the array and processing data.Preferably, an array of the invention further comprises a battery orother means adapted and arranged for providing electrical power to thearray or to objects or modules attached to the array.

In one aspect, the present technology can employ various kinds ofcomparisons of various kinds of brain activities with respect to thesame brain in order to determine the most advantageous locations orconformations of electrodes. Thus, the analyses of one or more brainactivities that are used to determine the correctly positioned orconformed electrodes and arrays of electrodes for delivering electricalNIBS can include many different parameters. Such parameters included,but are not limited to, the location, amplitude, timing, phase,frequency, and duration of one or more activities in one or more brainareas. The recorded brain activity thus obtained is especially usefulwhen the data recorded gives information about the consistency orcausation of amplitude relationships, time relationships, phaserelationships, frequency relationships, and the duration relationshipsacross multiple similar events processed by the brain, or across regionsin the brain.

In yet another series of embodiments of the invention, one or more kitsare provided. In some embodiments, a kit of the invention may compriseat least one array, software necessary to operate the array in alldesired aspects, and task software contained in operational connectionor within the array housing directed toward one or more specificpurposes. Task software in this context can be any software adapted andarranged for facilitating any task for which the kit is directed. Tasksoftware for use with the invention is preferably one or more from thegroup comprising language learning software, ability testing software,diagnostic software, and intervention software.

In yet another set of embodiments, the present invention includes one ormore networks, wherein each network comprises a plurality of variablyconfigurable electrode arrays, and wherein the plurality of arrays areadapted and arranged to be in operative communication with another whileone or a plurality of the arrays are in operational proximity to one ora plurality of the scalps of one or more subjects. A network of theinvention may further comprise a control module, wherein the controlmodule is adapted and arranged for facilitating a plurality of controlfunctions of the arrays and of the network. Preferable control functionsof the network include, as examples, one or more of oscillations of aparticular frequency, time varying functions on a single electrode andcoordinated with time varying functions on a plurality of electrodesthat can vary with respect to correlation, causality, duration, phase,latency, amplitude, and frequency. Moreover, multiple units may allowfor separate units to be stackable such that the number of stimulationchannels can be increased to multiples of the channel number in eachstimulator and made to work in combination when the devices are eithercollocated or remote from one another.

In some embodiments of the invention, one or more of the microprocessor,the software, and the data storage module are one or more of i) inoperative communication with one another, ii) in operative communicationwith one or more networks, and iii) in operative communication withhumans or computer systems external to the array. In a somewhat similarcontext, or more of the microprocessor, the software, and the datastorage module are in telemetric or other communication with acomputerized network, or with one or more other means for doing one ormore of a) recording data obtained or contained in connection with thearray, b) operating the array, and c) storing data contained or obtainedin connection with operation of the array.

In one embodiment, a kit of a device of the invention may comprise aclamshell-type housing adapted and arranged to contain a plurality, suchas inside 6, 8 or 10, electrodes, one or more preloaded gel packsadapted for facilitating all effective interface between the electrodesand the skin of the scalp, as well as electrodes, electrode holders, anda head frame. As another advantageous aspect of some preferredembodiments of the invention, the housing is provided with one or moremeans for operatively and reversibly containing one or more of themicroprocessor, the data storage module and the software means such thatsubstitute or interchangeable microprocessors, storage modules andsoftware means in operative communication with the array can beexchanged, replaced or substituted when desired. Thus, one or morearrays of the invention can be put to a myriad of selected uses.

In one advantageous set of aspects, many different types of software canbe used to direct or control the various functions, operationalparameters, and characteristics of the invention, including thefollowing, which are provided as examples, and not as limitations of thefunctions or uses of the invention. Thus, software for use with or inthe invention may comprise one or more of software for setting thestimulation duration across all electrodes of the array; software forsetting the stimulation intensity at each electrode; software forsetting the stimulation polarity at each electrode; software for settingthe stimulation DC offsets at each electrode; software for setting thetime varying function at each electrode; software for setting the rampup and ramp down times at each electrode; software for checking theimpedance at each electrode; and software for monitoring the impedanceat each electrode: software for controlling safety override voltages ateach electrode; software for setting the lockout time period across allelectrodes; software for effecting one or more electrode maintenanceroutines across all electrodes; software for checking one or morebattery parameters before stimulation begins; software for locking thesettings to prevent tampering with the software and certain settings ofthe device; software for operatively communicating with the arraysoftware interface for setting stimulation parameters; software foroperatively connecting a plurality of arrays to one another, andsoftware for performing finite element modeling.

Additional software includes one or more software for one or more ofdetermining and redetermining the optimal spatial location of one ormore electrodes with respect to the scalp and with respect to thehousing, software for one or more of determining and redetermining theoptimal polarity of each electrode at each location, software for one ormore of determining and redetermining the intensity of the currentdelivery at each electrode location, software for one or more ofdetermining and redetermining the time varying wave form with respect toeach electrode; software for generating time varying functions thatmimic one or more brain activities, software for detecting EEG signals,software for generating feedback to alter one or more electrical orstructural brain activities, software for interpreting and classifyingdetected EEG activity as a desired or an undesirable brain state, andsoftware for providing feedback to the subject in the form of one ormore types of electrical brain stimulation, as well as software meansfor one or more of determining and redetermining one or more tasks ofthe arrays.

As yet another characteristic of certain embodiments of the invention,one or more of the microprocessor, the data storage module and thesoftware can be reversibly provided in operation proximity to one ormore electrodes of the array. Thus, arrays of the invention can beprogrammed and reprogrammed by switching out various physical andsoftware components. In addition, one or more of the microprocessor, thedata storage module and the software can be permanently provided inoperation proximity to one or more electrodes of the array.

As yet other advantages of embodiments of the invention, the array ofone or more of the housing and electrodes can be adapted and arrangedfor determining the respective optimal operational parameters andconfigurations of one or more external scalp electrodes, pluralities ofelectrodes or electrode arrays with respect to a single subject brain.Moreover, one or more of the microprocessor, the data storage module andthe software can be adapted and arranged to be reconfigured duringoperation of the array on a subject. Thus, as arrays of the inventionare operating and communicating with various systems, their variousfunctions can be changed or redirected as wanted or needed.

As additional adaptive advantages and characteristics of someembodiments of the present invention, the present arrays can be providedin self-contained embodiments, or kits. Although many embodiments ofself-contained arrays are within the spirit and scope of the invention,typical embodiments include those that are provided as kits. Thus, atypical kit embodiment of the present variably configurable electrodearray would include at least one array, wherein the array comprises: atleast two electrodes, wherein each of the electrodes is operationallyconnected to the other electrodes, or to at least one microprocessor; ahousing adapted and arranged for variably positioning the electrodeswith respect to one another, and for variably positioning each of theelectrodes respectively in operational proximity to one or more regions,areas or points of a scalp of a subject upon which the array is placed;at least one microprocessor located in operational proximity to thehousing, wherein the microprocessor is adapted and arranged to processdata collected by means of the electrodes; and at least one data storagemodule located in operational proximity to the array, wherein the moduleis adapted and arranged to be operationally connectable to one or moreof the at least two electrodes and the at least one microprocessor; andat least one software suitable for storing software, wherein thesoftware is adapted and arranged for one or more of operating one ormore functions of the array, storing data collected by the array andprocessing data. It may also include software necessary to operate thearray in all desired aspects, and task software contained in operationalconnection or within the array housing directed toward one or morespecific purposes.

A self-contained embodiment of the invention may also include whereinthe task software is one or more from the group comprising languagelearning software, ability testing software, diagnostic software, andany other software adapted and arranged for effecting one or morediagnostic, evaluational teaching, and redirective tasks.

As yet another positive aspect, embodiments of the invention includealso where pluralities of electrodes or pluralities of arrays arenetworked plurality of variably configurable electrode arrays asdescribed herein, wherein the plurality of arrays are adapted andarranged to be in operative communication with one another while one ora plurality of the arrays are in operational proximity to one or aplurality of the scalps of one or more subjects. As in certain otherembodiments of the present invention, networked pluralities of arrays ofthe invention can be adapted and arranged to measure, test, evaluate,teach, redirect, record and assess numerous abilities, characteristics,values, capabilities and aspects of one or more brains.

In accordance with the several objects of the invention, a variablyconfigurable electrode array is provided in the context of effectingvarious methods, wherein one of the methods is a method for determiningthe optimum operational parameters of one or more neurologicalelectrodes or electrode arrays, the method comprising the steps oractions of: recording one or more brain activities of a subject toobtain one or more brain electrical activity patterns of the subjectbrain during i) one or more desirable brain states, and ii) one or moreundesirable brain states, to thereby obtain datasets with respect toeach activity, wherein the datasets with respect to the desirable brainstates and the undesirable brain states datasets are correlated; andthen evaluating any of the correlated datasets or patterns obtained withrespect to corresponding desirable and undesirable brain states toobtain one or more difference datasets; and then utilizing thedifference datasets to effect a determination of one or more targetregions, portions or locations of the subject brain. The present methodmay also comprise further the step or action of effecting stimulation ofthe determined target regions, portions or locations of the target brainwith electrical NIBS to the extent necessary to effect desired changesin the brain patterns or activities.

As another advantage of the present method, one or more of the polarity,intensity, and spatial distribution of the effected stimulation can beutilized to produce a desired excitation or inhibition of one or more ofthe regions, portions or locations of the target brain. Moreover, thestimulation is adapted and arranged to effect the maximal desiredinfluence at the one or more regions, portions or locations of thetarget brain such that changes in the brain effected by the NIBSinfluences the targets to move from one or more undesirable states toone or more desirable states.

In another significant aspect of many preferred embodiments of methodsof the present technology, finite element modeling is used to filter orrefine the datasets and images obtained by electrodes and arrays of theinvention. As examples, finite element modeling of one or more of thetarget brain, scalp, skull and associated tissues is utilized in orderto determine the most advantageous parameters of the various possibleconfigurations and variations of the present electrodes and arrays.

Method of the present technology may also utilize wherein the brainactivities are recorded by one or more of magnetoencephalography (MEG),electroencephalography (EEG), functional magnetic resonance imaging(fMRI), positron emission tomography (PET), single photon emissioncomputed tomography (SPECT), electrocorticography (ECOG), structuralmagnetic resonance imaging (sMRI), diffusion tensor imaging (DTI),magnetic resonance spectroscopy (MRS), and/or functional near infraredspectroscopy (fNIRS) during desirable and non-desirable brain states,i.e. expert vs. novice, highly attentive vs. non-attentive, awake vs.fatigued, correct responses vs. incorrect responses, injured vs.uninjured.

In accordance with the many objects of the present invention, methodsfor determining the optimal operational parameters and configurations ofone or more external scalp electrodes, pluralities of electrodes orelectrode arrays with respect to a single subject brain, are provided.In one significant embodiment, the method comprises the steps or actionsof: operating one or more of the electrodes or electrode arrays tocreate one or more recordings of activities, states, or structures of asubject brain to obtain data with respect to the one or more activities,states, or structures of the subject brain during one or more desirablebrain states, and one or more undesirable brain states, to therebycollect obtained datasets regarding each activity, state or structurewith respect to the desirable brain states and with respect to theundesirable brain states, wherein the obtained datasets are adaptable toone or more comparisons: then effecting one or a plurality ofcomparisons of the obtained datasets with respect to correspondingdesirable and undesirable brain states to obtain one or more differencedatasets; then evaluating the difference datasets to effect adetermination of one or more target regions, portions or locations ofthe subject brain. The present method may also include the further stepof utilizing the obtained datasets and the difference datasets to effectone or more redesigns or reconfigurations of the one or more externalelectrodes or electrode arrays to arrive at an improved or optimizedelectrode or electrode array.

As examples of the variability and adaptability of the present methods,electrodes and arrays, the one or more redesigns or reconfigurations canbe made with respect to many factors, functions and uses. These include,as examples, one or more of the three-dimensional relationships betweenor among the electrodes, pluralities of electrodes or electrode arrays,the three-dimensional relationships between or among the electrodes,pluralities of electrodes or electrode arrays, one or more electrodecarriers or frames, and the scalp upon which the electrodes, pluralitiesof electrodes or electrode arrays are placed.

This is also true with respect to those situations wherein theadaptations, redesigns or reconfigurations of the electrodes,pluralities of electrodes or electrode arrays are made with respect toone or more of the difference in images or patterns obtained, forexample, as part of the present methods and arrays, finite elementmodeling in which the brain regions, portions, locations, or structuresare selected in a brain virtualized in a finite element model can beused as a filter to determine the locations on the scalp whereelectrodes would be most effective in delivering current to theidentified brain area. Examples of parameters that can be indicated bythe finite element modeling include, as examples, the spatial locationof electrodes on the scalp, the polarity of the electrode at eachlocation, the intensity of the current delivery at each electrodelocation, and the time varying wave form at each electrode location.

The present method may also comprise the step or action of utilizing theimproved or optimized electrode, plurality of electrodes or electrodearray to stimulate the target brain to thereby test the design of theimproved electrode or electrode array and to obtain additional datasets;as well as the step of utilizing the additional datasets to furtherredesign or reconfigure the improved electrode or plurality ofelectrodes in an array to arrive at a final electrode or plurality ofelectrodes in an array.

In accordance with yet additional positive aspects and adaptations ofthe present technology, one of the present methods includes that fordetermining the optimal operational parameters and configurations of oneor more external scalp electrodes with respect to a plurality of subjectbrains, the method comprising the steps or actions of: creating one ormore records of one or more brain activities, states, or structures withrespect to the plurality of the subject brains to obtain data withrespect to one or more brain electrical activities of the plurality ofthe subject brains during i) one or more desirable brain states, and ii)one or more undesirable brain states, to thereby collect obtaineddatasets regarding each activity, state, or structure with respect tothe desirable brain states and with respect to the undesirable brainstates, wherein the obtained datasets are adaptable to one or morecomparisons; then effecting one or a plurality of comparisons of theobtained datasets with respect to corresponding desirable andundesirable brain states of the plurality of brains to obtain one ormore difference datasets; and then evaluating the difference datasets toeffect a determination of one or more target regions, portions orlocations of the plurality of subject brains.

The ng-TDCS may accordingly be utilized for a number of differentapplications. One such application is training where ng-TDCS may beadapted and arranged to compare the performance of novices and expertsto then target stimulation to facilitate the transition from novice toexpert. The ng-TDCS stimulation could be applied to classroom learningin the full spectrum of topics, e.g., to learning new languages,learning to perform a complex motor task, to entrance exams includingthose for different schools and a full spectrum of other entrance exams.A portable TDCS unit could also make training in a variety of sportspossible, e.g., swing training in golf, learning plays and defensivepatterns in football, basketball, soccer, etc.

Another example of an application for ng-TDCS may be for varioustreatments where the ng-TDCS may be adapted and arranged to be used toimage the brain when the behavior of the neurologically impairedindividual was desirable and again in states where the behavior wasundesirable. For example, when a person has high or low anxiety, when aperson with schizophrenia is hallucinating or not, when a person withautism is making eye contact or not, when a person with post-traumaticstress disorder is having a nightmare or not, when a person withmigraine headaches is in pain or not, when a person with chronic pain ishaving a painful experience or not, when a person with a phobia is in afearful state or not, when a person with epilepsy is having a seizure ornot, etc. Moreover, ng-TDCS could be used to aid in the transition fromundesirable to desirable behavioral states.

Yet another example of an application for ng-TDCS may be forrehabilitation where the ng-TDCS stimulation could be used in theretraining of compensatory strategies, e.g., after a stroke, headinjury, traumatic brain injury, brain surgery, etc.

Thus, in the same way, ng-TDCS compares novices and experts,neuroimaging could be performed on separate trials in the scanner(s)when performance is successful and when performance is unsuccessful. Forexample, in memory tasks the brain activity during incorrect responsescould be subtracted from the activity during correct responses. Thiswould show the brain regions that are critical for successfulperformance and these region(s) could be modeled with finite elementmodeling to generate electrode placements for ng-TDCS treatment thatfacilitate successful performance.

In addition, the effect of TDCS on the fractional anisotropy as measuredwith diffusion tensor imaging indicates that white matter tracts couldbe strengthened and perhaps even repaired in head injury and traumaticbrain injury where breaks in the white matter connections between brainareas are thought to be important in the observed deficits.

Yet another application may include decision making where ng-TDCS can beadapted and arranged to be used to facilitate decision making strategiesthat are advantageous in specific tasks. Intuitive, deductive, andinductive reasoning could be imaged in the scanner(s) to delineate thebrain structures critical to each type of decision making. Then thesepatterns of brain activation could be input into the finite elementmodeling routine to indicate the electrode positions that could be usedto influence brain networks to engage preferentially in type ofreasoning over others. Potential examples of this may include technicaltrading in the stock or commodities markets, shoot/no shoot training forlaw enforcement professionals, screening of baggage at airports,training to drive, detective work, military intelligence, surveillance,and reconnaissance operations, etc.

Yet another application may include enhanced response speed or accuracywhere ng-TDCS can be adapted and arranged to bias the brain networkstoward quick or careful responding to maximize speed or accuracy whenone strategy benefits the task more than the other. This could beapplied to technical trading in the commodities or stock markets,marksmanship, gaming, etc.

Yet another application may include reduction in distractions whereng-TDCS can similarly be adapted and arranged to aide in focus on asingle line of information to rapidly induce a flow state. This would bebeneficial in tasks where prolonged vigilance or focus is beneficialsuch as military intelligence, surveillance, and reconnaissanceoperations, gaming, or technical trading in the commodities or stockmarket, etc.

Yet another application may include treatment for natural declines anddisorders of aging where ng-TDCS can be adapted and arranged to aide inreversing or slowing age related memory decline as well as memorydecline in age related disorders such as dementia.

These particular applications for ng-TDCS are provided as examples andare not intended to be limiting. Other applications for ng-TDCS are, ofcourse, intended to be included within the scope of this disclosure.

All patents and publications referenced or mentioned herein areindicative of the levels of skill of those skilled in the art to whichthe invention pertains, and each such referenced patent or publicationis hereby incorporated by reference to the same extent as if it had beenincorporated by reference in its entirety individually or set forthherein in its entirety. Applicants reserve the light to physicallyincorporate into this specification any and all materials andinformation from any such cited patents or publications. The specificmethods and compositions described herein are representative ofpreferred embodiments and are exemplary and not intended as limitationson the scope of the invention. Other objects, aspects, and embodimentswill occur to those skilled in the art upon consideration of thisspecification, and are encompassed within the spirit of the invention asdefined by the scope of the claims. It will be readily apparent to oneskilled in the art that varying substitutions and modifications may bemade to the invention disclosed herein without departing from the scopeand spirit of the invention. The invention illustratively describedherein suitably may be practiced in the absence of any element orelements, or limitation or limitations, which is not specificallydisclosed herein as essential. The methods and processes illustrativelydescribed herein suitably may be practiced in differing orders of steps,and that they are not necessarily restricted to the orders of stepsindicated herein or in the claims. As used herein and in the appendedclaims, the singular forms “a,” “an,” and “the” include plural referenceunless the context clearly dictates otherwise. Thus, for example, areference to “a host cell” includes a plurality (for example, a cultureor population) of such host cells, and so forth.

Under no circumstances may the patent be interpreted to be limited tothe specific examples or embodiments or methods specifically disclosedherein. The terms and expressions that have been employed are used asterms of description and not of limitation, and there is no intent inthe use of such terms and express ions to exclude any equivalent of thefeatures shown and described or portions thereof, but it is recognizedthat various modifications are possible within the scope of theinvention as claimed. Thus, it will be understood that although thepresent invention has been specifically disclosed by preferredembodiments and optional features, modification and variation of theconcepts herein disclosed may be resorted to by those skilled in theart, and that such modifications and variations are considered to bewithin the Scope of this invention as defined by the appended claims.

The invention is described broadly and generically herein, while alsoproviding descriptions Figures, photo-images and diagrams of variousspecific or exemplary embodiments of elements or portions of theinvention. Each of the narrower species and subgeneric groupings fallingwithin the generic disclosure also form part of the invention. Thisincludes the generic description of the invention with a proviso ornegative limitation removing any subject matter from the genus,regardless of whether or not the excised material is specificallyrecited herein.

What is claimed is:
 1. A method of treating a subject, comprising:recording low level brain activity of the subject corresponding to a lowperformance state; recording high level brain activity of the subjectcorresponding to a high performance state; determining a differencebetween the low performance state and the high performance state toproduce a difference image; modeling the difference image to determine acorresponding pattern of electrical activity; identifying one or moreregions of maximal current density on a scalp surface corresponding tothe pattern of electrical activity; and stimulating the one or moreregions on the scalp surface such that the corresponding regions of thebrain are stimulated.
 2. The method of claim 1 wherein recording lowlevel brain activity and high level brain activity comprisesneuroimaging the brain of the subject.
 3. The method of claim 2 whereinneuroimaging the brain comprises imaging via MEG, EEG, fMRI, PET, SPECT,ECOG, fNIRS, sMRI, DTI, or MRS.
 4. The method of claim 1 whereindetermining a difference comprises subtracting areas common to both thelow level brain activity and high level brain activity such that thedifference image comprises areas of brain activity that change betweenthe low performance and high performance states.
 5. The method of claim1 wherein modeling the difference image comprises modeling via a finiteelement model to calculate the pattern of electrical activity.
 6. Themethod of claim 1 wherein stimulating the one or more regions comprisesnoninvasively applying a stimulation to the scalp surface.
 7. The methodof claim 6 wherein the stimulation is selected from the group consistingof transcranial magnetic stimulation (TMS), repetitive TMS (rTMS),pulsed electromagnetic fields (PEMF), transcranial alternating currentstimulation (TACS), transcranial random noise stimulation (TRNS), timevarying electrical stimulation (TVES), and ultrasound brain stimulation(UBS).
 8. The method of claim 1 wherein stimulating the one or moreregions comprises applying a single electrode polarity to the scalpsurface.
 9. The method of claim 8 wherein applying a single electrodepolarity comprises applying at least one anode to enhance brain activityor at least one cathode to suppress brain activity.
 10. The method ofclaim 1 wherein stimulating the one or more regions comprises applyingthe stimulation over a ramp up period, a treatment period, and a rampdown period.
 11. The method of claim 10 wherein the ramp up periodranges from 10 sees to 15 mms.
 12. The method of claim 10 wherein theramp up period is variable.
 13. The method of claim 10 wherein the rampdown period is variable.
 14. The method of claim 10 wherein thetreatment period ranges from 0.1 mins to 60 mms.
 15. The method of claim10 wherein the treatment period comprises applying time varyingstimulation having a frequency of 0 to 10,000 Hz.
 16. The method ofclaim 10 wherein the treatment period has a current which ranges from0.1 rnA to 4 rnA.
 17. The method of claim 10 wherein the ramp downperiod ranges from 10 sees to 15 mms.
 18. The method of claim 1 whereinstimulating comprises positioning at least one electrode upon the scalpsurface.
 19. The method of claim 18 wherein positioning at least oneelectrode comprises securing the at least one electrode to the head ofthe subject.
 20. The method of claim 19 further comprising introducing aconductive medium within a cavity or channel between the at least oneelectrode and the scalp surface.
 21. The method of claim 1 whereinstimulating the one or more regions comprises reconfiguring an electrodeassembly in two or more electrode components for positioning relative tothe corresponding regions of the brain.
 22. The method of claim 21wherein positioning the two or more electrode components comprisessupporting the components via a head frame configured to individuallyposition the components relative to the regions of the brain.
 23. Themethod of claim 1 wherein stimulating the one or more regions comprisesdriving a plurality of channels where each channel provides a currentsource independent from one another.
 24. The method of claim 23 whereina voltage level of each channel is controlled by an arbitrary waveforminput into a controller.
 25. The method of claim 23 further comprisingmonitoring for an open circuit in each of the plurality of channels. 26.The method of claim 23 further comprising monitoring an impedance overthe plurality of channels to determine a mean impedance value.
 27. Themethod of claim 26 further comprising adjusting the current source overan electrode-to-scalp connection impedance range of 4 to 40,000 Ohms.28. The method of claim 1 further comprising transmitting data relatingto the stimulation to a device located remotely from a controller. 29.The method of claim 1 further comprising locking out for a predeterminedperiod of time any further stimulation once a treatment session has beencompleted. 30-64. (canceled)